Eur J Pharmacol. 2009 May 12; Wang SB, Tian S, Yang F, Yang HG, Yang XY, Du GHThe present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 312-8Liang A, Wang J, Xue B, Li C, Liu T, Zhao Y, Cao C, Yi YOBJECTIVE: To investigate hepatoxicity and nephrotoxicity of cinnabar to provide the scientific basis for safe uses in clinic. METHOD: Maximally tolerated dose of cinnabar (MTD) was tested by single oral administration. Chronic toxicity of cinnabar at different dose level (0.025, 0.05, 0.1, 0.4, 0.8 g x kg(-1) x d(-1)) corresponding to 1/2, 1, 2, 8, 16 times of clinic doses of cinnabar was investigated. The rats were treated with the cinnabar through oral administration once a day for successive 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of cinnabar and no-observed adverse effect level (NOAEL) were evaluated. RESULT: For the content of 98.1% total Hg and 21.5 microg x g(-1) absoluble Hg, MTD of cinnabar with oral administration was 24 g x kg(-1) (corresponding to 516 microg x kg(-1) absoluble Hg), equivalent to 3,000 times of clinical daily dose for an adult, and no obvious adverse effect was showed at this dose. Cinnabar can cause kidney and liver pathological changes when it is repeatedly administrated for over 30 days. The kidney was more sensitive to cinnabar than liver. Based on repeated dose toxicity study, NOAELs were 0.1, 0.05 g x kg(-1) x d(-1)) respectively for 30 day and 90 day treatment, and those were approximately accumulative intake of absoluble Hg 64.5 microg x kg(-1) and 96.76 microg x kg(-1). Thus, for safe use of cinnabar, the acceptable daily intake (ADI) of cinnabar was 0.0009-0.0017 g x kg(-1) x d(-1), namely daily dose 0.05-0.1 g for an adult with body weight about 60 kg. Considering the difference of drug sensitivity and lifecircle between human and rats, we suggest that cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used for no longer than 2 weeks at daily dose 0.05-0.1 g. CONCLUSION: Long term use of cinnabar can cause kidney and liver pathological change, so the dose and administration duration should be limited. The suggestion is as follows: cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used less than 2 weeks at the daily dose below 0.05-0.1 g.